Physical training of Zucker rats: lack of alleviation of muscle insulin resistance

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Abstract
Genetically obese, insulin-resistant Zucker rats (fa/fa) and their lean littermates (Fa/?) were divided into exercise-trained and sedentary control groups at 4-5 wk of age. Exercise-trained animals were subjected to a progressive program of treadmill running for 6-8 wk. Forty-four hours after the last training session, basal and insulin-stimulated glucose metabolism was studied in incubated strips (25-35 mg) of soleus muscle. In some groups of animals, 2-deoxyglucose uptake and specific binding of 125I-labeled insulin were measured. Glucose tolerance was measured with i.v. infusion of 0.5 g glucose/kg body wt of lean animals. In lean rats, training was associated with increased glucose tolerance but no change in pre- or postglucose insulin concentrations. Basal and maximally stimulated glucose metabolism in soleus muscle was not changed, but there was increased sensitivity to insulin manifested by a shift to the left of the insulin dose-response curve of glycolysis. No consistent changes in glycogen synthesis, glucose transport or insulin binding were observed. In obese rats, training was also associated with increased glucose tolerance. Basal plasma insulin was unchanged, but post-glucose concentrations were 28% lower. Insulin sensitivity and responsiveness of soleus muscle in vitro were decreased markedly in obese animals and were not improved by training. Physical training can improve glucose tolerance in both lean and obese Zucher rats and enhance muscle sensitivity to insulin in lean animals. The training program used did not prevent or reverse the marked insulin resistance of muscle that develops in obese Zucker rats.